Research Papers:

Cyclin A2 regulates homologous recombination DNA repair and sensitivity to DNA damaging agents and poly(ADP-ribose) polymerase (PARP) inhibitors in human breast cancer cells

Wei Wei Gu, Jie Lin and Xing Yu Hong _

PDF  |  HTML  |  How to cite

Oncotarget. 2017; 8:90842-90851. https://doi.org/10.18632/oncotarget.20412

Metrics: PDF 2095 views  |   HTML 2122 views  |   ?  


Wei Wei Gu2, Jie Lin1 and Xing Yu Hong1

1 Department of Vascular Surgery, China-Japan Union Hospital of Jilin University, Changchun, China

2 Department of Hepatopancreatobility Surgery, China-Japan Union Hospital of Jilin University, Changchun, China

Correspondence to:

Xing Yu Hong, email:

Keywords: cyclin A2, homologous recombination repair, double-strand breaks, MRE11, RAD51

Received: June 15, 2017 Accepted: July 25, 2017 Published: August 24, 2017


Defects in homologous recombination (HR) repair are found in breast cancers. Intriguingly, breast cancers with defective HR show increased sensitivity to DNA crosslinking agents and poly(ADP-ribose) polymerase (PARP) inhibitors. As such, genes that can affect HR functions have been of high interest in studies aiming to develop biomarkers for predicting response to treatment with these agents. Cyclin A2 is a key component of the core cell cycle machinery. However, whether cyclin A2 dysfunctions could cause HR defect and mediate sensitivity to DNA damaging agents remain unclear. Here we show that loss of cyclin A2 causes high rates of double-strand breaks (DSB) in MCF-7 and MDA-MB-231 cells. The increased DSB was due to defective HR-mediated repair of the breaks, resulting from reduced MRE11 and RAD51 proteins. Cyclin A2 mediates MRE11 abundance through its MRE11 mRNA binding property and RAD51 abundance through inhibition of proteasome degradation of RAD51. Moreover, cyclin A2 depletion hypersensitized the cells to DNA damaging agents, such as cisplatin and melphalan. Our results demonstrate novel roles for cyclin A2 in regulating HR repair and determining sensitivity to DNA cross linkers and PARP inhibitors in breast cancer cells.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 20412